Search

The use of tranexamic acid for postpartum hemorrhage has entered obstetric practice globally with the evidence-based expectation of saving lives. This improvement in the care of women with postpartum hemorrhage has come at a price. For the anesthetist, having tranexamic acid ampoules close at hand would seem an obvious strategy to facilitate its use during caesarean delivery, an important setting for severe hemorrhage. Tragically, we have identified a number of recent instances of inadvertent intrathecal administration of tranexamic acid instead of local anesthetic for spinal anesthesia. Reported cases of this catastrophic error appear to be increasing. The profound neurotoxicity of tranexamic acid causes rapid-onset convulsions, with mortality of 50%. How can these tragic errors be averted? Drug safety alerts have been issued by the US Food and Drug Administration and the World Health Organization, but that is not enough. We recommend extensive dissemination of information to raise awareness of this potential hazard; and local hospital protocols to ensure that tranexamic acid is stored separately from anesthetic drugs, preferably outside the operating room and with an auxiliary warning label. Implementation of safety strategies on a very large scale will be needed to ensure that the life-saving potential of tranexamic acid is not eclipsed by drug error mortality.

Preterm birth is the leading cause of death in newborns and children. Tocolytic drugs aim to delay preterm birth by suppressing uterine contractions to allow time for administration of corticosteroids for fetal lung maturation, magnesium sulphate for neuroprotection, and transport to a facility with appropriate neonatal care facilities. However, there is still uncertainty about their effectiveness and safety.To estimate relative effectiveness and safety profiles for different classes of tocolytic drugs for delaying preterm birth, and provide rankings of the available drugs.We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov (21 April 2021) and reference lists of retrieved studies.We included all randomised controlled trials assessing effectiveness or adverse effects of tocolytic drugs for delaying preterm birth. We excluded quasi- and non-randomised trials. We evaluated all studies against predefined criteria to judge their trustworthiness.At least two review authors independently assessed the trials for inclusion and risk of bias, and extracted data. We performed pairwise and network meta-analyses, to determine the relative effects and rankings of all available tocolytics. We used GRADE to rate the certainty of the network meta-analysis effect estimates for each tocolytic versus placebo or no treatment.This network meta-analysis includes 122 trials (13,697 women) involving six tocolytic classes, combinations of tocolytics, and placebo or no treatment. Most trials included women with threatened preterm birth, singleton pregnancy, from 24 to 34 weeks of gestation. We judged 25 (20%) studies to be at low risk of bias. Overall, certainty in the evidence varied. Relative effects from network meta-analysis suggested that all tocolytics are probably effective in delaying preterm birth compared with placebo or no tocolytic treatment. Betamimetics are possibly effective in delaying preterm birth by 48 hours (risk ratio (RR) 1.12, 95% confidence interval (CI) 1.05 to 1.20; low-certainty evidence), and 7 days (RR 1.14, 95% CI 1.03 to 1.25; low-certainty evidence). COX inhibitors are possibly effective in delaying preterm birth by 48 hours (RR 1.11, 95% CI 1.01 to 1.23; low-certainty evidence). Calcium channel blockers are possibly effective in delaying preterm birth by 48 hours (RR 1.16, 95% CI 1.07 to 1.24; low-certainty evidence), probably effective in delaying preterm birth by 7 days (RR 1.15, 95% CI 1.04 to 1.27; moderate-certainty evidence), and prolong pregnancy by 5 days (0.1 more to 9.2 more; high-certainty evidence). Magnesium sulphate is probably effective in delaying preterm birth by 48 hours (RR 1.12, 95% CI 1.02 to 1.23; moderate-certainty evidence). Oxytocin receptor antagonists are probably effective in delaying preterm birth by 48 hours (RR 1.13, 95% CI 1.05 to 1.22; moderate-certainty evidence), are effective in delaying preterm birth by 7 days (RR 1.18, 95% CI 1.07 to 1.30; high-certainty evidence), and possibly prolong pregnancy by 10 days (95% CI 2.3 more to 16.7 more). Nitric oxide donors are probably effective in delaying preterm birth by 48 hours (RR 1.17, 95% CI 1.05 to 1.31; moderate-certainty evidence), and 7 days (RR 1.18, 95% CI 1.02 to 1.37; moderate-certainty evidence). Combinations of tocolytics are probably effective in delaying preterm birth by 48 hours (RR 1.17, 95% CI 1.07 to 1.27; moderate-certainty evidence), and 7 days (RR 1.19, 95% CI 1.05 to 1.34; moderate-certainty evidence). Nitric oxide donors ranked highest for delaying preterm birth by 48 hours and 7 days, and delay in birth (continuous outcome), followed by calcium channel blockers, oxytocin receptor antagonists and combinations of tocolytics. Betamimetics (RR 14.4, 95% CI 6.11 to 34.1; moderate-certainty evidence), calcium channel blockers (RR 2.96, 95% CI 1.23 to 7.11; moderate-certainty evidence), magnesium sulphate (RR 3.90, 95% CI 1.09 to 13.93; moderate-certainty evidence) and combinations of tocolytics (RR 6.87, 95% CI 2.08 to 22.7; low-certainty evidence) are probably more likely to result in cessation of treatment. Calcium channel blockers possibly reduce the risk of neurodevelopmental morbidity (RR 0.51, 95% CI 0.30 to 0.85; low-certainty evidence), and respiratory morbidity (RR 0.68, 95% CI 0.53 to 0.88; low-certainty evidence), and result in fewer neonates with birthweight less than 2000 g (RR 0.49, 95% CI 0.28 to 0.87; low-certainty evidence). Nitric oxide donors possibly result in neonates with higher birthweight (mean difference (MD) 425.53 g more, 95% CI 224.32 more to 626.74 more; low-certainty evidence), fewer neonates with birthweight less than 2500 g (RR 0.40, 95% CI 0.24 to 0.69; low-certainty evidence), and more advanced gestational age (MD 1.35 weeks more, 95% CI 0.37 more to 2.32 more; low-certainty evidence). Combinations of tocolytics possibly result in fewer neonates with birthweight less than 2500 g (RR 0.74, 95% CI 0.59 to 0.93; low-certainty evidence). In terms of maternal adverse effects, betamimetics probably cause dyspnoea (RR 12.09, 95% CI 4.66 to 31.39; moderate-certainty evidence), palpitations (RR 7.39, 95% CI 3.83 to 14.24; moderate-certainty evidence), vomiting (RR 1.91, 95% CI 1.25 to 2.91; moderate-certainty evidence), possibly headache (RR 1.91, 95% CI 1.07 to 3.42; low-certainty evidence) and tachycardia (RR 3.01, 95% CI 1.17 to 7.71; low-certainty evidence) compared with placebo or no treatment. COX inhibitors possibly cause vomiting (RR 2.54, 95% CI 1.18 to 5.48; low-certainty evidence). Calcium channel blockers (RR 2.59, 95% CI 1.39 to 4.83; low-certainty evidence), and nitric oxide donors probably cause headache (RR 4.20, 95% CI 2.13 to 8.25; moderate-certainty evidence).Compared with placebo or no tocolytic treatment, all tocolytic drug classes that we assessed (betamimetics, calcium channel blockers, magnesium sulphate, oxytocin receptor antagonists, nitric oxide donors) and their combinations were probably or possibly effective in delaying preterm birth for 48 hours, and 7 days. Tocolytic drugs were associated with a range of adverse effects (from minor to potentially severe) compared with placebo or no tocolytic treatment, although betamimetics and combination tocolytics were more likely to result in cessation of treatment. The effects of tocolytic use on neonatal outcomes such as neonatal and perinatal mortality, and on safety outcomes such as maternal and neonatal infection were uncertain.

Background/aims Effective labour monitoring is integral to intrapartum care. Yet, to date, tools to facilitate this have not reached their potential. This study aims to explore midwives' initial reactions to the latest World Health Organization labour care guide, which is a replacement to the existing partograph, to enable adaptations to be made and to inform implementation strategies. Methods This was a qualitative study that used interviews and focus groups to gather data from a convenience sample of midwife delegates from six sub-Saharan Africa countries who were attending a midwifery conference in Malawi. Data were analysed thematically. Results A total of 43 participants participated; six focus groups and 12 individual interviews were conducted. Participants expressed both positive and negative views of the guide. Three main themes were found. The theme ‘sticking to what is familiar’ demonstrated reluctance to change; ‘chart based on usual or optimum practice’ suggested that midwives wanted a chart that reflects the routine care provided as opposed to the evidence-based care they should provide; and ‘measures for effective implementation’ highlighted the importance of having carefully considered and robust strategies for implementing the guide. Conclusions This rapid evaluation provided a snapshot of midwives' initial reactions to the new labour care guide. Although the existing partograph has not reached its full potential, midwives showed a reluctance to change it for something new. Feedback from participants has been fed into the development phase of the guide, informing its presentation, contents and field testing.

The WHO ACTION-I trial, the largest placebo-controlled trial on antenatal corticosteroids (ACS) efficacy and safety to date, reaffirmed the benefits of ACS on mortality reduction among early preterm newborns in low-income settings. We discuss here lessons learned from ACTION-I trial that are relevant to a strategy for ACS implementation to optimize impact. Key elements included (i) gestational age dating by ultrasound (ii) application of appropriate selection criteria by trained obstetric physicians to identify women with a likelihood of preterm birth for ACS administration; and (iii) provision of a minimum package of care for preterm newborns in facilities. This strategy accurately identified a large proportion of women who eventually gave birth preterm, and resulted in a 16% reduction in neonatal mortality from ACS use. Policy-makers, programme managers and clinicians are encouraged to consider this implementation strategy to effectively scale and harness the benefits of ACS in saving preterm newborn lives.

OBJECTIVES To evaluate uterine tamponade devices' effectiveness for atonic refractory postpartum haemorrhage (PPH) after vaginal birth and the effect of including them in institutional protocols. SEARCH STRATEGY PubMed, EMBASE, CINAHL, LILACS, POPLINE, from inception to January 2021. STUDY SELECTION Randomised and non-randomised comparative studies. OUTCOMES Composite outcome including surgical interventions (artery ligations, compressive sutures or hysterectomy) or maternal death, and hysterectomy. RESULTS All included studies were at high risk of bias. The certainty of the evidence was rated as very low to low. One randomised study measured the effect of the condom-catheter balloon compared with standard care and found unclear results for the composite outcome (relative risk [RR] 2.33, 95% CI 0.76-7.14) and hysterectomy (RR 4.14, 95% CI 0.48-35.93). Three comparative studies assessed the effect of including uterine balloon tamponade in institutional protocols. A stepped wedge cluster randomised controlled trial suggested an increase in the composite outcome (RR 4.08, 95% CI 1.07-15.58) and unclear results for hysterectomy (RR 4.38, 95% CI 0.47-41.09) with the use of the condom-catheter or surgical glove balloon. One non-randomised study showed unclear effects on the composite outcome (RR 0.33, 95% CI 0.11-1.03) and hysterectomy (RR 0.49, 95% CI 0.04-5.38) after the inclusion of the Bakri balloon. The second non-randomised study found unclear effects on the composite outcome (RR 0.95, 95% CI 0.32-2.81) and hysterectomy (RR 1.84, 95% CI 0.44-7.69) after the inclusion of Ebb or Bakri balloon. CONCLUSIONS The effect of uterine tamponade devices for the management of atonic refractory PPH after vaginal delivery is unclear, as is the role of the type of device and the setting. TWEETABLE ABSTRACT Unclear effects of uterine tamponade devices and their inclusion in institutional protocols for atonic refractory PPH after vaginal delivery.

Women who have had repeated miscarriages often have uncertainties about the cause, the likelihood of recurrence, the investigations they need, and the treatments that might help. Health-care policy makers and providers have uncertainties about the optimal ways to organise and provide care. For this Series paper, we have developed recommendations for practice from literature reviews, appraisal of guidelines, and a UK-wide consensus conference that was held in December, 2019. Caregivers should individualise care according to the clinical needs and preferences of women and their partners. We define a minimum set of investigations and treatments to be offered to couples who have had recurrent miscarriages, and urge health-care policy makers and providers to make them universally available. The essential investigations include measurements of lupus anticoagulant, anticardiolipin antibodies, thyroid function, and a transvaginal pelvic ultrasound scan. The key treatments to consider are first trimester progesterone administration, levothyroxine in women with subclinical hypothyroidism, and the combination of aspirin and heparin in women with antiphospholipid antibodies. Appropriate screening and care for mental health issues and future obstetric risks, particularly preterm birth, fetal growth restriction, and stillbirth, will need to be incorporated into the care pathway for couples with a history of recurrent miscarriage. We suggest health-care services structure care using a graded model in which women are offered online health-care advice and support, care in a nurse or midwifery-led clinic, and care in a medical consultant-led clinic, according to clinical needs.

Background While Doppler ultrasound screening is beneficial for women with high-risk pregnancies, there is insufficient evidence on its benefits and harms in low- and unselected-risk pregnancies. This may be related to fewer events of abnormal Doppler flow, however the prevalence of absent or reversed end diastolic flow (AEDF or REDF) in such women is unknown. In this systematic review, we aimed to synthesise available data on the prevalence of AEDF or REDF. Methods We searched PubMed, Embase, CINAHL, CENTRAL and Global Index Medicus with no date, setting or language restrictions. All randomized or non-randomized studies reporting AEDF or REDF prevalence based on Doppler assessment of umbilical arterial flow > 20 weeks’ gestation were eligible. Two authors assessed eligibility and extracted data on primary (AEDF and REDF) and secondary (fetal, perinatal, and neonatal mortality, caesarean section) outcomes, with results presented descriptively. Results A total of 42 studies (18,282 women) were included. Thirty-six studies reported zero AEDF or REDF cases. However, 55 AEDF or REDF cases were identified from just six studies (prevalence 0.08% to 2.13%). Four of these studies were in unselected-risk women and five were conducted in high-income countries. There was limited evidence from low- and middle-income countries. Conclusions Evidence from largely observational studies in higher-income countries suggests that AEDF and REDF are rare among low- and unselected-risk pregnant women. There are insufficient data from lower-income countries and further research is required.

The WHO ACTION-I trial demonstrated that dexamethasone significantly reduced neonatal mortality when administered to women at risk of early preterm birth in low-resource countries. We conducted a secondary analysis to determine how these benefits can be optimised, by evaluating the effect of dexamethasone compared to placebo on newborn mortality and severe respiratory distress outcomes at different administration-to-birth intervals, and identifying the interval with the greatest benefits.The WHO ACTION-I trial was a multi-country, individually-randomised, parallel-group, double-blind, placebo-controlled trial. It was conducted in 29 hospitals across Bangladesh, India, Kenya, Nigeria, and Pakistan. Women with a viable singleton or multiple pregnancy who presented to participating hospitals at a gestational age of 26 weeks 0 days-33 weeks 6 days and who were at risk of imminent preterm birth were eligible. In this secondary analysis, 2638 women and their newborns treated with single course of dexamethasone or placebo were analysed. Multivariate logistic regression was used to assess the effect of dexamethasone versus placebo on neonatal death, stillbirth or neonatal death, and severe respiratory distress at 24 h and at 168 h, by administration-to-birth interval (from 0 through 28 days), adjusting for gestational age at first dose. We used relative risks to identify the administration-to-birth interval with the greatest benefits of dexamethasone compared to placebo on the newborn outcomes.Between 24 December 2017 and 21 November 2019, 2852 women and their 3070 babies were enrolled in the WHO ACTION-I trial; 1332 women (1464 babies) in the dexamethasone group and 1306 women (1440 babies) in the placebo group were included in this secondary analysis. Neonatal mortality risk was lower with increasing time between initiating dexamethasone and birth, achieving peak mortality reduction by days 13 and 14 and then diminishing as the interval approached 28 days, regardless of gestational age at administration. For other outcomes, the overall pattern of risk reduction extending into the second week was consistent with that of neonatal death.In women at risk of preterm birth prior to 34 weeks' gestation, the neonatal benefits of antenatal dexamethasone appear to increase with longer administration-to-birth intervals than previously thought. This knowledge can support clinical assessment and estimation of the risks of adverse preterm newborn outcomes at the time of birth, and the potential benefits of antenatal dexamethasone treatment for a known administration-to-birth interval.Bill and Melinda Gates Foundation; World Health Organization.

Preterm birth is a leading cause of neonatal mortality and morbidity, and imposes high health and societal costs. Antenatal corticosteroids (ACS) to accelerate fetal lung maturation are commonly used in conjunction with tocolytics for arresting preterm labour in women at risk of imminent preterm birth.We conducted a systematic review on the cost-effectiveness of ACS and/or tocolytics as part of preterm birth management. We systematically searched MEDLINE and Embase (December 2021), as well as a maternal health economic evidence repository collated from NHS Economic Evaluation Database, EconLit, PubMed, Embase, CINAHL and PsycInfo, with no date cutoff. Eligible studies were economic evaluations of ACS and/or tocolytics for preterm birth. Two reviewers independently screened citations, extracted data on cost-effectiveness and assessed study quality using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement.35 studies were included: 11 studies on ACS, eight on tocolytics to facilitate ACS administration, 12 on acute and maintenance tocolysis, and four studies on a combination of ACS and tocolytics. ACS was cost-effective prior to 34 weeks' gestation, but economic evidence on ACS use at 34-37 weeks was conflicting. No single tocolytic was identified as the most cost-effective. Studies disagreed on whether ACS and tocolytic in combination were cost-saving when compared to no intervention.ACS use prior to 34 weeks' gestation appears cost-effective. Further studies are required to identify what (if any) tocolytic option is most cost-effective for facilitating ACS administration, and the economic consequences of ACS use in the late preterm period.UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), a cosponsored programme executed by WHO.

IntroductionFew interventions exist to address the high burden of stillbirths in apparently healthy pregnant women in low- and middle-income countries (LMICs). To establish whether a trial on the impact of routine Doppler screening in a low-risk obstetric population is warranted, we determined the prevalence of abnormal fetal umbilical artery resistance indices among low-risk pregnant women using a low-cost Doppler device in five LMICs.MethodsWe conducted a multicentre, prospective cohort study in Ghana, India, Kenya, Rwanda and South Africa. Trained nurses or midwives performed a single, continuous-wave Doppler screening using the Umbiflow device for low-risk pregnant women (according to local guidelines) between 28 and 34 weeks’ gestation. We assessed the prevalence of abnormal (raised) resistance index (RI), including absent end diastolic flow (AEDF), and compared pregnancy and health service utilisation outcomes between women with abnormal RI versus those with normal RI.ResultsOf 7151 women screened, 495 (6.9%) had an abnormal RI, including 14 (0.2%) with AEDF. Caesarean section (40.8% vs 28.1%), labour induction (20.5% vs 9.0%) and low birth weight (ConclusionA single Doppler screening of low-risk pregnant women in LMICs using the Umbiflow device can detect a large number of fetuses at risk of growth restriction and consequent adverse perinatal outcomes. Many perinatal deaths could potentially be averted with appropriate intervention strategies.Trial registration numberCTRI/2018/07/01486.

ObjectivesTo assess the rates of SARS-CoV-2 positivity in babies born to mothers with SARS-CoV-2 infection, the timing of mother-to-child transmission and perinatal outcomes, and factors associated with SARS-CoV-2 status in offspring.DesignLiving systematic review and meta-analysis.Data sourcesMajor databases between 1 December 2019 and 3 August 2021.Study selectionCohort studies of pregnant and recently pregnant women (including after abortion or miscarriage) who sought hospital care for any reason and had a diagnosis of SARS-CoV-2 infection, and also provided data on offspring SARS-CoV-2 status and risk factors for positivity. Case series and case reports were also included to assess the timing and likelihood of mother-to-child transmission in SARS-CoV-2 positive babies.Data extractionTwo reviewers independently extracted data and assessed study quality. A random effects model was used to synthesise data for rates, with associations reported using odds ratios and 95% confidence intervals. Narrative syntheses were performed when meta-analysis was inappropriate. The World Health Organization classification was used to categorise the timing of mother-to-child transmission (in utero, intrapartum, early postnatal).Results472 studies (206 cohort studies, 266 case series and case reports; 28 952 mothers, 18 237 babies) were included. Overall, 1.8% (95% confidence interval 1.2% to 2.5%; 140 studies) of the 14 271 babies born to mothers with SARS-CoV-2 infection tested positive for the virus with reverse transcriptase polymerase chain reaction (RT-PCR). Of the 592 SARS-CoV-2 positive babies with data on the timing of exposure and type and timing of tests, 14 had confirmed mother-to-child transmission: seven in utero (448 assessed), two intrapartum (18 assessed), and five during the early postnatal period (70 assessed). Of the 800 SARS-CoV-2 positive babies with outcome data, 20 were stillbirths, 23 were neonatal deaths, and eight were early pregnancy losses; 749 babies were alive at the end of follow-up. Severe maternal covid-19 (odds ratio 2.4, 95% confidence interval 1.3 to 4.4), maternal death (14.1, 4.1 to 48.0), maternal admission to an intensive care unit (3.5, 1.7 to 6.9), and maternal postnatal infection (5.0, 1.2 to 20.1) were associated with SARS-CoV-2 positivity in offspring. Positivity rates using RT-PCR varied between regions, ranging from 0.1% (95% confidence interval 0.0% to 0.3%) in studies from North America to 5.7% (3.2% to 8.7%) in studies from Latin America and the Caribbean.ConclusionSARS-CoV-2 positivity rates were found to be low in babies born to mothers with SARS-CoV-2 infection. Evidence suggests confirmed vertical transmission of SARS-CoV-2, although this is likely to be rare. Severity of maternal covid-19 appears to be associated with SARS-CoV-2 positivity in offspring.Systematic review registrationPROSPERO CRD42020178076.Readers’ noteThis article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.

Background: Uterine tamponade is widely promoted for treating refractory postpartum hemorrhage (PPH); however, its cost‐effectiveness may vary depending on unit costs and setting. Objective: To review available data on cost‐effectiveness of uterine tamponade devices when used for PPH treatment. Search strategy: PubMed and EMBASE were searched (1980 to January 2020), as well as the National Health Services Economic Evaluation database from inception (1995) to March 2015. Selection criteria: Eligible studies were any type of economic evaluation, or effective‐ ness studies that provided cost or economic data. Data collection and analysis: Two reviewers independently screened studies, extracted data, and assessed quality. Main results: Eleven studies using a range of devices (condom catheter, uterine suc‐ tion devices, Bakri, Inpress, Ellavi) were identified. Cost of condom catheter devices or kits ranged from US$0.64 to US$6, whereas purpose‐designed device costs were up to US$400. Two studies that took a health system perspective assessed the cost‐ effectiveness of using uterine balloon tamponade and suggested that it was highly cost‐ effective because of the low cost per disability‐adjusted life‐year averted, although both used effect estimates from case series. Conclusions: Evidence on the cost‐effectiveness of uterine tamponade devices was limited and not generalizable. Rigorous economic evaluations based on updated effect estimates are needed. Fil: Vogel, Joshua P.. Monash University; Australia Fil: Wilson, Alyce N.. Burnet Institute; Australia Fil: Scott, Nick. Monash University; Australia. Burnet Institute; Australia Fil: Widmer, Mariana. Organizacion Mundial de la Salud; Argentina Fil: Althabe, Fernando. Organizacion Mundial de la Salud; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina Fil: Oladapo, Olufemi T.. Organizacion Mundial de la Salud; Argentina

BACKGROUND: Current intramuscular magnesium dosing regimens in low and middle-income countries are based on indirect absorption parameters to inform pharmacokinetic and pharmacodynamic response. OBJECTIVE: To determine if therapeutic serum magnesium levels are obtained in women with severe preeclampsia receiving intramuscular administration of magnesium sulfate using the Pritchard regimen and to compare the key pharmacokinetic variables to those previously published. STUDY DESIGN: Serum magnesium levels were obtained at multiple time points at baseline and after magnesium sulfate administration from women with severe preeclampsia receiving the standard Pritchard regimen for seizure prophylaxis at Bayero University, Kano, Nigeria. The pharmacokinetic profiles were constructed for the study cohort and the updated pharmacokinetic model was compared with the one that was previously published. RESULTS: A total of 80 blood samples were collected from 20 women with severe preeclampsia (45 collected before childbirth and 35 collected after childbirth). After 11.5 hours of magnesium sulfate administration, 63% of women in the cohort had serum magnesium levels of ≥2.0 mmol/L. Data from women receiving the Pritchard regimen combined with data from women previously modeled after the receipt of intravenous magnesium sulfate were adequately described using a 2-compartment model with first-order absorption and linear elimination from the central compartment. All structural pharmacokinetic parameters including clearance, central volume of distribution, peripheral volume of distribution, and intercompartment clearance were adjusted for maternal weight, and the clearance was further adjusted for serum creatinine level and antepartum or postpartum status. The simulated pharmacokinetic profiles of the updated pharmacokinetic model and the previously published pharmacokinetic model are similar. In previously published pharmacokinetic modeling, absorption rate constant=0.32 and absolute bioavailability=0.86. In the updated pharmacokinetic model, absorption rate constant=0.45 and absolute bioavailability=0.91. CONCLUSION: These data support the use of the Pritchard regimen as acceptable to achieve therapeutic serum magnesium levels and support the reported simulation of serum magnesium levels and eclampsia response associated with different intramuscular regimens.

Background Preterm birth is a leading cause of death among children under five years. Previous estimates indicated global preterm birth rate of 10.6% (14.8 million neonates) in 2014. We aim to update preterm birth estimates at global, regional, and national levels for the period 2010 to 2019. Methods Preterm birth is defined as a live birth occurring before 37 completed gestational weeks, or Discussion Accurate measurement of preterm birth is challenging in many countries given incomplete or unavailable data from national administrative sources, compounded by limited gestational age assessment during pregnancy to define preterm birth. Up-to-date modelled estimates will be an important resource to measure the global burden of preterm birth and to inform policies and programs especially in settings with a high burden of neonatal mortality. Trial registration PROSPERO registration: CRD42021237861.

OBJECTIVE: Clinical trials evaluating pharmacological and non-pharmacological treatment of COVID-19, either excluded pregnant women or included very few women. Unlike the numerous systematic reviews on prevalence, symptoms and adverse outcomes of COVID-19 in pregnancy, there are very few on the effects of treatment on maternal and neonatal outcomes in pregnancy. We undertook a systematic review of all published and unpublished studies on the effects of pharmacological and non-pharmacological interventions for COVID-19 on maternal and neonatal pregnancy outcomes. DATA SOURCES: We performed a systematic literature search of the following databases: Medline, Embase, Cochrane database, WHO (World Health Organization) COVID-19 database, China National Knowledge Infrastructure (CNKI), and Wanfang databases from 1 December 2019 to 1 December 2020. STUDY ELIGIBILITY CRITERIA: Studies were only included if they involved pregnant or postnatal women who were exposed to pregnancy specific interventions like the mode of delivery and type of anaesthesia, pharmacological or non-pharmacological interventions. STUDY APPRAISAL AND SYNTHESIS METHODS: We first screened the titles and abstracts of studies and then assessed the full text of the selected studies in detail for eligibility. Data on study design, population, type of screening for COVID-19, country, hospital, country status (high or low and middle income), treatment given (mode of delivery, type of anaesthesia, type of pharmacological and non-pharmacological treatment was extracted. The pre-defined maternal outcomes we collected were mode of delivery (vaginal or by caesarean section), severe or critical COVID-19 (as defined by the authors), symptomatic COVID-19, maternal death, maternal hospital admission, ICU admission, mechanical ventilation, ECMO and maternal pneumonia. The pre-defined neonatal outcomes we extracted were preterm birth (

The WHO in collaboration with the Nigeria Federal Ministry of Health, established a nationwide electronic data platform across referral-level hospitals. We report the burden of maternal, foetal and neonatal complications and quality and outcomes of care during the first year.Data were analysed from 76,563 women who were admitted for delivery or on account of complications within 42 days of delivery or termination of pregnancy from September 2019 to August 2020 across the 54 hospitals included in the Maternal and Perinatal Database for Quality, Equity and Dignity programme.Participating hospitals reported 69,055 live births, 4,498 stillbirths and 1,090 early neonatal deaths. 44,614 women (58·3%) had at least one pregnancy complication, out of which 6,618 women (8·6%) met our criteria for potentially life-threatening complications, and 940 women (1·2%) died. Leading causes of maternal death were eclampsia (This nationwide programme for routine data aggregation shows that maternal and perinatal mortality reduction strategies in Nigeria require a multisectoral approach. Several lives could be saved in the short term by addressing key predictors of death, including gaps in the coverage of internationally recommended interventions such as companionship in labour and use of labour monitoring tool.This work was funded by MSD for Mothers; and UNDP/UNFPA/ UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), a co-sponsored programme executed by the World Health Organization (WHO).

Maternal morbidities are precursors to maternal mortality as well as potential causes of life time disability and poor quality of life. This study aimed to determine the pattern and spectrum of life-threatening maternal morbidities seen in tertiary reproductive health facilities in Nigeria. All cases of severe maternal outcome (SMO), maternal near-misses (MNM), or maternal death (MD), attending 42 tertiary hospitals across all geopolitical zones of Nigeria were prospectively identified using the WHO criteria over a period of 14 months. The main outcome measures were the incidence and outcome of severe maternal outcome by geopolitical regions of Nigeria. The participating hospitals recorded a total of 4383 severe maternal outcomes out of which were 3285 maternal near-misses and 998 maternal deaths. The proportion of maternal near-miss was similar across all the geopolitical zones but the maternal mortality ratio was highest in the southwestern zone (1,552) and least in the northcentral zone (750) of the country. Haemorrhage was the leading cause of severe maternal morbidities followed by hypertensive disorders of pregnancy. The mortality index of about 41% using the organ dysfunction criterion was triple the figures from other parts of the world. The findings reflect poor obstetric care in the tertiary hospitals in Nigeria. The health facilities in the country urgently need to be revamped.

Background There are questions about the use of the ‘one‐centimetre per hour rule’ as a valid benchmark for assessing the adequacy of labour progress. Objectives To determine the accuracy of the alert (1‐cm/hour) and action lines of the cervicograph in the partograph to predict adverse birth outcomes among women in first stage of labour. Search strategy PubMed, EMBASE, CINAHL, POPLINE, Global Health Library, and reference lists of eligible studies. Selection criteria Observational studies and other study designs reporting data on the correlation between the alert line status of women in labour and the occurrence of adverse birth outcomes. Data collection and analysis Two reviewers at a time independently identified eligible studies and independently abstracted data including population characteristics and maternal and perinatal outcomes. Main results Thirteen studies in which 20 471 women participated were included in the review. The percentage of women crossing the alert line varied from 8 to 76% for all maternal or perinatal outcomes. No study showed a robust diagnostic test accuracy profile for any of the selected outcomes. Conclusions This systematic review does not support the use of the cervical dilatation over time (at a threshold of 1 cm/h during active first stage) to identify women at risk of adverse birth outcomes. Tweetable abstract Alert line of partograph does not identify women at risk of adverse birth outcomes., Tweetable abstract Alert line of partograph does not identify women at risk of adverse birth outcomes.

Summary Background There is ongoing debate on the clinical benefits of antibiotic prophylaxis for reducing pelvic infection after miscarriage surgery. We aimed to study the cost-effectiveness of antibiotic prophylaxis in the surgical management of miscarriage in low-income countries. Methods We did an incremental cost-effectiveness analysis using data from 3412 women recruited to the AIMS trial, a randomised, double-blind, placebo-controlled trial designed to evaluate the effectiveness of antibiotic prophylaxis in the surgical management of miscarriage in Malawi, Pakistan, Tanzania, and Uganda. Economic evaluation was done from a health-care-provider perspective on the basis of the outcome of cost per pelvic infection avoided within 2 weeks of surgery. Pelvic infection was broadly defined by the presence of clinical features or the clinically identified need to administer antibiotics. We used non-parametric bootstrapping and multilevel random effects models to estimate incremental mean costs and outcomes. Decision uncertainty was shown via cost-effectiveness acceptability frontiers. The AIMS trial is registered with the ISRCTN registry, number ISRCTN97143849. Findings Between June 2, 2014, and April 26, 2017, 3412 women were assigned to receive either antibiotic prophylaxis (1705 [50%] of 3412) or placebo (1707 [50%] of 3412) in the AIMS trial. 158 (5%) of 3412 women developed pelvic infection within 2 weeks of surgery, of whom 68 (43%) were in the antibiotic prophylaxis group and 90 (57%) in the placebo group. There is 97–98% probability that antibiotic prophylaxis is a cost-effective intervention at expected thresholds of willingness-to-pay per additional pelvic infection avoided. In terms of post-surgery antibiotics, the antibiotic prophylaxis group was US$0·27 (95% CI −0·49 to −0·05) less expensive per woman than the placebo group. A secondary analysis, a sensitivity analysis, and all subgroup analyses supported these findings. Antibiotic prophylaxis, if implemented routinely before miscarriage surgery, could translate to an annual total cost saving of up to $1·4 million across the four participating countries and up to $8·5 million across the two regions of sub-Saharan Africa and south Asia. Interpretation Antibiotic prophylaxis is more effective and less expensive than no antibiotic prophylaxis. Policy makers in various settings should be confident that antibiotic prophylaxis in miscarriage surgery is cost-effective. Funding UK Medical Research Council, Wellcome Trust, and the UK Department for International Development.

Background Antenatal corticosteroids (ACS) have long been regarded as a cornerstone intervention in mitigating the adverse effects of a preterm birth. However, the safety and efficacy of ACS in hospitals in low-resource countries has not been established in an efficacy trial despite their widespread use. Findings of a large cluster-randomized trial in six low- and middle-income countries showed that efforts to scale up ACS use in low-resource settings can lead to harm. There is equipoise regarding the benefits and harms of ACS use in hospitals in low-resource countries. This randomized controlled trial aims to determine whether ACS are safe and efficacious when given to women at risk of imminent birth in the early preterm period, in hospitals in low-resource countries. Methods/design The trial design is a parallel, two-arm, double-blind, individually randomized, placebo-controlled trial of ACS (dexamethasone) for women at risk of imminent preterm birth. The trial will recruit 6018 women in participating hospitals across five low-resource countries (Bangladesh, India, Kenya, Nigeria and Pakistan). The primary objectives are to compare the efficacy of dexamethasone with placebo on survival of the baby and maternal infectious morbidity. The primary outcomes are: 1) neonatal death (to 28 completed days of life); 2) any baby death (any stillbirth postrandomization or neonatal death); and 3) a composite outcome to assess possible maternal bacterial infections. The trial will recruit eligible, consenting pregnant women from 26 weeks 0 days to 33 weeks 6 days gestation with confirmed live fetuses, in whom birth is planned or expected within 48 h. The intervention comprises a regimen of intramuscular dexamethasone sodium phosphate. The comparison is an identical placebo regimen (normal saline). A total of 6018 women will be recruited to detect a reduction of 15% or more in neonatal deaths in a two-sided 5% significance test with 90% power (including 10% loss to follow-up). Discussion Findings of this trial will guide clinicians, programme managers and policymakers on the safety and efficacy of ACS in hospitals in low-resource countries. The trial findings will inform updating of the World Health Organization’s global recommendations on ACS use. Trial registration ACTRN12617000476336. Registered on 31 March 2017. Electronic supplementary material The online version of this article (10.1186/s13063-019-3488-z) contains supplementary material, which is available to authorized users.

Magnesium sulfate is the anticonvulsant of choice for eclampsia prophylaxis and treatment; however, the recommended dosing regimens are costly and cumbersome and can be administered only by skilled health professionals. The objectives of this study were to develop a robust exposure‐response model for the relationship between serum magnesium exposure and eclampsia using data from large studies of women with preeclampsia who received magnesium sulfate, and to predict eclampsia probabilities for standard and alternative (shorter treatment duration and/or fewer intramuscular injections) regimens. Exposure‐response modeling and simulation were applied to existing data. A total of 10 280 women with preeclampsia who received magnesium sulfate or placebo were evaluated. An existing population pharmacokinetic model was used to estimate individual serum magnesium exposure. Logistic regression was applied to quantify the serum magnesium area under the curve‐eclampsia rate relationship. Our exposure‐response model‐estimated eclampsia rates were comparable to observed rates. Several alternative regimens predicted magnesium peak concentration

BACKGROUND: Several uterotonic options exist for prevention of postpartum hemorrhage (PPH); hence, cost-effectiveness is an important decision-making criterion affecting uterotonic choice. OBJECTIVE: To conduct a systematic review of cost-effectiveness of uterotonics for PPH prevention to support a WHO guideline update. SEARCH STRATEGY: We searched major databases from 1980 to June 2018 and the National Health Services Economic Evaluation (NHS EED) database from inception (1995) to March 2015 for eligible studies. SELECTION CRITERIA: We included comparative economic evaluations, cost-utility analyses, and resource-utilization studies. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed studies and extracted data organized by birth mode and setting. MAIN RESULTS: We included 15 studies across all income categories that compared misoprostol versus no uterotonic (five studies) or versus oxytocin (one study), carbetocin versus oxytocin (eight studies), and one study comparing numerous uterotonics. In specific low-resource contexts, we found reasonably good evidence that misoprostol was cost-effective compared with no uterotonic. In the context of cesarean delivery, carbetocin was more cost favorable than oxytocin but certainty of this evidence was low. CONCLUSIONS: Evidence on the cost-effectiveness of various uterotonic agents was not generalizable. As the number of competing uterotonics increases, rigorous economic evaluations including contextual factors are needed.

OBJECTIVE To compare severe maternal outcomes (SMOs) from two multi-centre surveys in Nigerian hospitals, and to evaluate how the SMO burden affects quality of secondary and tertiary hospital care. DESIGN Two facility-based surveys of women experiencing SMO (maternal near-miss or maternal deaths). SETTING Sixteen secondary and five tertiary facilities in Nigeria [WHO Multi-Country Survey on Maternal and Newborn Health (WHOMCS)] and 42 public tertiary facilities in Nigeria (Nigeria Near-Miss and Maternal Death Survey). POPULATION 371 women in WHOMCS-Nigeria and 2449 women in Nigeria Near-Miss and Maternal Death Survey who experienced SMO. METHODS Secondary analysis and comparison of SMO data from two surveys, stratified by facility level. MAIN OUTCOME MEASURES Maternal mortality ratio (MMR) per 100 000 livebirths (LB), maternal near-miss (MNM) ratio per 1000 LB, SMO ratio per 1000 LB and mortality index (deaths/SMO). RESULTS Maternal mortality ratio and mortality indices were highest in tertiary facilities of the WHOMCS-Nigeria (706 per 100 000; 26.7%) and the Nigeria Near-Miss and Maternal Death Survey (1088 per 100 000; 40.8%), and lower in secondary facilities of the WHOMCS-Nigeria (593 per 100 000; 17.9%). The MNM ratio and SMO ratio were highest in secondary WHOMCS-Nigeria facilities (27.2 per 1000 LB; 33.1 per 1000 LB). CONCLUSIONS Tertiary-level facilities in Nigeria experience unacceptably high maternal mortality rates, but secondary-level facilities had a proportionately higher burden of severe maternal outcomes. Common conditions with a high mortality index (postpartum haemorrhage, eclampsia, and infectious morbidities) should be prioritised for action. Surveillance using SMO indicators can guide quality improvement efforts and assess changes over time. TWEETABLE ABSTRACT 2820 Nigerian women with severe maternal outcomes: high mortality in tertiary level hospitals, higher burden in secondary level.

Objective To investigate the prevalence of life-threatening complications related to pregnancies with abortive outcome and the associated health service events and performance in Nigerian public tertiary hospitals. Design Secondary analysis of a nationwide cross-sectional study. Setting Forty-two tertiary hospitals. Population Women admitted for pregnancy-related complications. Methods All cases of severe maternal outcomes (SMO: maternal near-miss or death) due to abortive pregnancy complications (defined as spontaneous or induced abortion, and ectopic pregnancy) were prospectively identified over 1 year using uniform identification criteria. Main outcome measures Prevalence of SMO, mortality index (% maternal death/SMO), case fatality rate, time until death after admission, and health service performance. Results Of 5779 women admitted with abortive pregnancy complications, 444 (7.9%) experienced an SMO: 366 maternal near-misses and 78 maternal deaths. Intra-hospital maternal mortality ratio from complicated abortive pregnancy outcome was 85/100 000 live births. Case fatality rate was worst for abortion-related infections (19.1%). A quarter of maternal deaths occurred on the same day of admission; however, the peak time of occurrence of death was 3-7 days of admission. Women experiencing cardiovascular, renal or coagulation organ dysfunction were less likely to survive. Higher level of maternal education and closer residence to a health facility improved chance of maternal survival. Conclusions Abortive outcome remains a major contributor to SMO in Nigeria. Although early hospital presentation by women is critical to surviving abortive pregnancy complications, improved, appropriate, and timely management is essential to enhance maternal survival. Tweetable abstract 78 maternal deaths and 366 near-misses occurred from abortions and ectopic pregnancies in 42 Nigerian referral hospitals in 1 year.

Background Preterm birth-related complications are the leading cause of death in newborns and children under 5. Health outcomes of preterm newborns can be improved with appropriate use of antenatal corticosteroids (ACSs) to promote fetal lung maturity, tocolytics to delay birth, magnesium sulphate for fetal neuroprotection, and antibiotics for preterm prelabour rupture of membranes. However, there are wide disparities in the rate and consistency in the use of these interventions across settings, which may underlie the differential health outcomes among preterm newborns. We aimed to assess factors (barriers and facilitators) affecting the appropriate use of ACS, tocolytics, magnesium sulphate, and antibiotics to improve preterm birth management. Methods and findings We conducted a mixed-methods systematic review including primary qualitative, quantitative, and mixed-methods studies. We searched MEDLINE, EMBASE, CINAHL, Global Health, and grey literature from inception to 16 May 2022. Eligible studies explored perspectives of women, partners, or community members who experienced preterm birth or were at risk of preterm birth and/or received any of the 4 interventions, health workers providing maternity and newborn care, and other stakeholders involved in maternal care (e.g., facility managers, policymakers). We used an iterative narrative synthesis approach to analysis, assessed methodological limitations using the Mixed Methods Appraisal Tool, and assessed confidence in each qualitative review finding using the GRADE-CERQual approach. Behaviour change models (Theoretical Domains Framework; Capability, Opportunity, and Motivation (COM-B)) were used to map barriers and facilitators affecting appropriate use of these interventions. We included 46 studies from 32 countries, describing factors affecting use of ACS (32/46 studies), tocolytics (13/46 studies), magnesium sulphate (9/46 studies), and antibiotics (5/46 studies). We identified a range of barriers influencing appropriate use of the 4 interventions globally, which include the following: inaccurate gestational age assessment, inconsistent guidelines, varied knowledge, perceived risks and benefits, perceived uncertainties and constraints in administration, confusion around prescribing and administering authority, and inadequate stock, human resources, and labour and newborn care. Women reported hesitancy in accepting interventions, as they typically learned about them during emergencies. Most included studies were from high-income countries (37/46 studies), which may affect the transferability of these findings to low- or middle-income settings. Conclusions In this study, we identified critical factors affecting implementation of 4 interventions to improve preterm birth management globally. Policymakers and implementers can consider these barriers and facilitators when formulating policies and planning implementation or scale-up of these interventions. Study findings can inform clinical preterm birth guidelines and implementation to ensure that barriers are addressed, and enablers are reinforced to ensure these interventions are widely available and appropriately used globally.

The physical and psychological effect of miscarriage is commonly underappreciated. The journey from diagnosis of miscarriage, through clinical management, to supportive aftercare can be challenging for women, their partners, and caregivers. Diagnostic challenges can lead to delayed or ineffective care and increased anxiety. Inaccurate diagnosis of a miscarriage can result in the unintended termination of a wanted pregnancy. Uncertainty about the therapeutic effects of interventions can lead to suboptimal care, with variations across facilities and countries. For this Series paper, we have developed recommendations for practice from a literature review, appraisal of guidelines, and expert group discussions. The recommendations are grouped into three categories: (1) diagnosis of miscarriage, (2) prevention of miscarriage in women with early pregnancy bleeding, and (3) management of miscarriage. We recommend that every country reports annual aggregate miscarriage data, similarly to the reporting of stillbirth. Early pregnancy services need to focus on providing an effective ultrasound service, as it is central to the diagnosis of miscarriage, and be able to provide expectant management of miscarriage, medical management with mifepristone and misoprostol, and surgical management with manual vacuum aspiration. Women with the dual risk factors of early pregnancy bleeding and a history of previous miscarriage can be recommended vaginal micronised progesterone to improve the prospects of livebirth. We urge health-care funders and providers to invest in early pregnancy care, with specific focus on training for clinical nurse specialists and doctors to provide comprehensive miscarriage care within the setting of dedicated early pregnancy units.

Background Postpartum hemorrhage (PPH) is the leading cause of maternal death worldwide. When PPH occurs, early identification of bleeding and prompt management using evidence-based guidelines, can avert most PPH-related severe morbidities and deaths. However, adherence to the World Health Organization recommended practices remains a critical challenge. A potential solution to inefficient and inconsistent implementation of evidence-based practices is the application of a ‘clinical care bundle’ for PPH management. A clinical care bundle is a set of discrete, evidence-based interventions, administered concurrently, or in rapid succession, to every eligible person, along with teamwork, communication, and cooperation. Once triggered, all bundle components must be delivered. The E-MOTIVE project aims to improve the detection and first response management of PPH through the implementation of the “E-MOTIVE” bundle, which consists of (1) Early PPH detection using a calibrated drape, (2) uterine Massage, (3) Oxytocic drugs, (4) Tranexamic acid, (5) Intra Venous fluids, and (6) genital tract Examination and escalation when necessary. The objective of this paper is to describe the protocol for the formative phase of the E-MOTIVE project, which aims to design an implementation strategy to support the uptake of this bundle into practice. Methods We will use behavior change and implementation science frameworks [e.g. capability, opportunity, motivation and behavior (COM-B) and theoretical domains framework (TDF)] to guide data collection and analysis, in Kenya, Nigeria, South Africa, Sri Lanka, and Tanzania. There are four methodological components: qualitative interviews; surveys; systematic reviews; and design workshops. We will triangulate findings across data sources, participant groups, and countries to explore factors influencing current PPH detection and management, and potentially influencing E-MOTIVE bundle implementation. We will use these findings to develop potential strategies to improve implementation, which will be discussed and agreed with key stakeholders from each country in intervention design workshops. Discussion This formative protocol outlines our strategy for the systematic development of the E-MOTIVE implementation strategy. This focus on implementation considers what it would take to support roll-out and implementation of the E-MOTIVE bundle. Our approach therefore aims to maximize internal validity in the trial alongside future scalability, and implementation of the E-MOTIVE bundle in routine practice, if proven to be effective. Trial registration: ClinicalTrials.gov: NCT04341662 Supplementary Information The online version contains supplementary material available at 10.1186/s12978-021-01162-3., Plain language summary Excessive bleeding after birth is the leading cause of maternal death globally. The World Health Organization (WHO) has recommended several treatment options for bleeding after birth. However, these treatments are not used regularly, or consistently for all women. A key underlying issue is that it is challenging for health workers to identify when women are bleeding too much, because measuring the amount of blood loss is difficult. Maternal health experts have proposed a new clinical ‘care bundle’ for caring for women with excessive bleeding after birth. A care bundle is a way to group together multiple treatments (e.g. 3–5 treatments). These treatments are then given to the woman at the same time, or one after another in quick succession, and supported by strategies to improve teamwork, communication, and cooperation. This is a research protocol for the preliminary phase of our study (“E-MOTIVE”), which means that it is a description of what we plan to do and how we plan to do it. The aim of our study is to develop a strategy for how we will test whether the E-MOTIVE bundle works through collaborative activities with midwives and doctors in five countries (Kenya, Nigeria, South Africa, Sri Lanka, and Tanzania) to develop a strategy for how we will test whether the E-MOTIVE bundle works. We plan to do this by conducting interviews and surveys with midwives and doctors, and reviewing other research conducted on PPH to understand what works in different settings. We will discuss our research findings in a workshop, with midwives and doctors in the study countries to co-create a strategy that will work for them, based on their needs and preferences. Supplementary Information The online version contains supplementary material available at 10.1186/s12978-021-01162-3.

The partograph is the most commonly used labour monitoring tool in the world. However, it has been used incorrectly or inconsistently in many settings. In 2018, a WHO expert group reviewed and revised the design of the partograph in light of emerging evidence, and they developed the first version of the Labour Care Guide (LCG). The objective of this study was to explore opinions of skilled health personnel on the first version of the WHO Labour Care Guide.Skilled health personnel (including obstetricians, midwives and general practitioners) of any gender from Africa, Asia, Europe and Latin America were identified through a large global research network. Country coordinators from the network invited 5 to 10 mid-level and senior skilled health personnel who had worked in labour wards anytime in the last 5 years. A self-administered, anonymous, structured, online questionnaire including closed and open-ended questions was designed to assess the clarity, relevance, appropriateness of the frequency of recording, and the completeness of the sections and variables on the LCG.A total of 110 participants from 23 countries completed the survey between December 2018 and January 2019. Variables included in the LCG were generally considered clear, relevant and to have been recorded at the appropriate frequency. Most sections of the LCG were considered complete. Participants agreed or strongly agreed with the overall design, structure of the LCG, and the usefulness of reference thresholds to trigger further assessment and actions. They also agreed that LCG could potentially have a positive impact on clinical decision-making and respectful maternity care. Participants disagreed with the value of some variables, including coping, urine, and neonatal status.Future end-users of WHO Labour Care Guide considered the variables to be clear, relevant and appropriate, and, with minor improvements, to have the potential to positively impact clinical decision-making and respectful maternity care.ANTECEDENTES: El partograma es la herramienta para el monitoreo del trabajo de parto más utilizada a nivel mundial. Sin embargo, en muchos entornos se utiliza de manera incorrecta o inconsistente. En 2018, un grupo de expertos de la OMS evaluó y modificó el diseño del partograma teniendo en cuenta la nueva evidencia científica, y elaboró la primera versión de la Guía para la Atención del Trabajo de Parto. El objetivo de este estudio fue explorar las perspectivas y opiniones de los profesionales de la salud sobre la primera versión de la Guía para la Atención del Trabajo de Parto. MéTODOS: Se identificó a profesionales de salud de servicios de maternidad (incluidos obstetras, parteras profesionales y médicos generalistas) de cualquier género de África, Asia, Europa y América Latina a través de una red de investigación internacional. Los coordinadores de países de la red invitaron entre 5 y 10 profesionales con nivel de experiencia media o avanzada que hubieran trabajado en servicios de maternidad en los últimos 5 años. Se diseñó un cuestionario en línea, autoadministrado, anónimo y estructurado que incluía preguntas cerradas y abiertas para evaluar la claridad, la pertinencia, la adecuación de la frecuencia de registro y la exhaustividad de las secciones y variables de la Guía para la Atención del Trabajo de Parto.Un total de 110 participantes de 23 países completaron la encuesta entre diciembre de 2018 y enero de 2019. Las variables incluidas en la Guía para la Atención del Trabajo de Parto se consideraron en general claras, pertinentes y con una frecuencia de registro apropiada. La mayoría de las secciones de la Guía para la Atención del Trabajo de Parto se consideraron completas. Los participantes estuvieron de acuerdo o muy de acuerdo con el diseño general, la estructura de la Guía para la Atención del Trabajo de Parto, y la utilidad de los umbrales de referencia para desencadenar evaluaciones y acciones adicionales. También estuvieron de acuerdo en que la Guía para la Atención del Trabajo de Parto tendrá un impacto positivo en la toma de decisiones clínicas y en el cuidado respetuoso. Los participantes no estuvieron de acuerdo con algunos parámetros propuestos en la Guía para la Atención del Trabajo de Parto, incluyendo el manejo de la situación por parte de las mujeres, parámetros urinarios y el estado neonatal.Los futuros usuarios de la Guía para la Atención del Trabajo de Parto consideraron que las variables eran claras, pertinentes y apropiadas, y que, con pequeñas mejoras, podría tener un impacto positivo en la toma de decisiones clínicas y la atención respetuosa del parto.RéSUMé: CONTEXTE: Le partogramme est l'outil de suivi du travail le plus couramment utillis dans le monde. Cependant, il est utilisé de façon incorrecte ou non uniforme dans de nombreux contextes. En 2018, un groupe d'experts de l'OMS a examiné et révisé la conception du partogramme à la lumière de nouvelles données et a développé la première version du Guide de Gestion du Travail. L'objectif de cette étude était d'explorer les points de vue et les opinions du personnel de santé qualifié sur la première version du Guide de Gestion du Travail de l'OMS. MéTHODES: Un vaste réseau mondial de recherche a permis d'identifier le personnel de santé qualifié (y compris des obstétriciens, des sages-femmes et des médecins généralistes) des deux sexes, en Afrique, Asie, Europe et en Amérique latine. Les coordinateurs nationaux du réseau ont invité entre 5 et 10 personnels de santé qualifiés de niveau intermédiaire à supérieur, et ayant travaillé dans des services de maternité à au cours des 5 dernières années. Un questionnaire en ligne, structuré, anonyme et à remplir soi-même, comprenant des questions fermées et ouvertes, a été conçu pour évaluer la clarté, la pertinence, la convenance de la fréquence d'enregistrement et l’intégrité des variables du Guide de Gestion du Travail. RéSULTATS: Au total, 110 participants de 23 pays ont répondu à l'enquête entre décembre 2018 et janvier 2019. Les variables incluses dans le Guide de Gestion du Travail ont t généralement considérées claires, pertinentes et avec une fréquence d'enregistrement appropriée. La plupart des sections du Guide de Gestion du Travail sont considérées complètes. Les participants ont approuvé ou fortement approuvé le concept générale, la structure du Guide de Gestion du Travail et l'utilité des seuils de référence pour déclencher une évaluation et des actions supplémentaires. Ils ont également convenu que le Guide de Gestion du Travail aura potentiellement un impact positif sur les prise de décisions cliniques et les soins maternels respectueux. Les personnes interrogées ont exprimé leur désaccord avec la valeur de certaines variables, notamment la capacité d'adaptation, l'urine et l'état néonatal. CONCLUSIONS: Les futurs utilisateurs du le Guide de Gestion du Travail ont estimé que les variables étaient claires, pertinentes et appropriées, et qu'elles pourraient avoir un impact positif sur la prise de décision clinique et les soins de maternit respectueux, moyennant quelques améliorations mineures.

Inclusion of pregnant women in COVID-19 clinical trials would allow evaluation of effective therapies that might improve maternal health, pregnancy, and birth outcomes, and avoid the delay of developing treatment recommendations for pregnant women. We explored the inclusion of pregnant women in treatment trials of COVID-19 by reviewing ten international clinical trial registries at two timepoints in 2020. We identified 155 COVID-19 treatment studies of non-biological drugs for the April 7-10, 2020 timepoint, of which 124 (80%) specifically excluded pregnant women. The same registry search for the July 10-15, 2020 timepoint, yielded 722 treatment studies, of which 538 (75%) specifically excluded pregnant women. We then focused on studies that included at least one of six drugs (remdesivir, lopinavir-ritonavir, interferon beta, corticosteroids, chloroquine and hydroxychloroquine, and ivermectin) under evaluation for COVID-19. Of 176 such studies, 130 (74%) listed pregnancy as an exclusion criterion. Of 35 studies that evaluated high-dose vitamin treatment for COVID-19, 27 (77%) excluded pregnant women. Despite the surge in treatment studies for COVID-19, the proportion excluding pregnant women remains consistent. Exclusion was not well justified as many of the treatments being evaluated have no or low safety concerns during pregnancy. Inclusion of pregnant women in clinical treatment trials is urgently needed to identify effective COVID-19 treatment for this population.

In 1972, two landmark papers in this journal described the partograph,1,2 a chart designed to provide finite referral criteria for midwives working in peripheral clinics who needed to refer women in labour to Harare Hospital, Zimbabwe (then Rhodesia). This innovation coincided with influential reports from the National Maternity Hospital in Dublin of the ‘active management of labour’ (early amniotomy, proactive use of oxytocin and one‐to‐one nursing care) with the objective of achieving birth within a limited time frame.3 The partograph was globally adopted, and has been used as part of the assessment of labour progress for nearly half a century. It was recommended by the World Health Organization (WHO) in the early 1990s as a routine tool for displaying the progress of labour. Despite its global acceptance, utilization and correct completion rates as low as 31% and 3% respectively, have been reported.

Additional file 2. Online questionnaire.

Additional file 4. Findings from open-ended questions.

Additional file 1: Appendix S1. PRISMA checklist.

Additional file 4. Findings from open-ended questions.

Additional file 2: Appendix S2. Search strategy.

Additional file 1. First version of the LCG.

Additional file 2: Appendix S2. Search strategy.

Additional file 4: Appendix S4. Quality assessments.

Additional file 3. Methodological details.

Additional file 4: Appendix S4. Quality assessments.